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Physiologically relevant forms of Tc- and Re-pyrophosphate radioactive tracers and the basis of their transthyretin amyloid sensitivity

Title: Physiologically relevant forms of Tc- and Re-pyrophosphate radioactive tracers and the basis of their transthyretin amyloid sensitivity
Authors: Kevin Zsolt Simon; Kende Attila Béres; Attila Farkas; Nándor Papp; Andrea Bodor; Veronika Harmat; Dávid Papp; Maria Gracheva; Máté Sulyok-Eiler; András Perczel; László Kótai; Dóra K. Menyhárd
Source: Scientific Reports, Vol 16, Iss 1 (2026)
Publisher Information: Nature Portfolio
Publication Year: 2026
Collection: Directory of Open Access Journals: DOAJ Articles
Subject Terms: Medicine; Science
Description: $${^{99\text {m}}}$$ Technetium Pyrophosphate ( $${^{99\text {m}}}$$ Tc-PYP(Sn)) is a commonly used radioactive tracer, with a long history of use in diagnosing bone-related diseases and a newfound purpose in differentiating ATTR and AL amyloidoses. Despite its ubiquity, basic aspects like its composition and structure are as of yet undetermined, and its method of binding to ATTR amyloid fibrils is likewise hitherto unknown. This complicates the diagnostic process, as it introduces inexplicable losses of sensitivity in some ATTR and AL variants. In this paper we report the results of our comprehensive investigation into the physiologically active structure of Tc-PYP and its closely related, but experimentally more approachable counterpart, Re-PYP, built on a robust theoretical basis and backed up by multiple spectroscopic methods (focusing on the rhenium analogue). We conclude that the Re/Tc-PYP tracers possess a flexible geometry, but ultimately appear as octahedral Re(IV)/Tc(IV) diaqua dipyrophosphate complexes under physiological conditions, and predict that this structure is the reason for the high affinity of $$\phantom{0}^{99m}$$ Tc-PYP for certain amyloids.
Document Type: article in journal/newspaper
Language: English
Relation: https://doi.org/10.1038/s41598-026-35746-5; https://doaj.org/toc/2045-2322; https://doaj.org/article/2722dc77242740e292033e77eb7b703e
DOI: 10.1038/s41598-026-35746-5
Availability: https://doi.org/10.1038/s41598-026-35746-5; https://doaj.org/article/2722dc77242740e292033e77eb7b703e
Accession Number: edsbas.BE23EC21
Database: BASE